Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival

Charlotte Aaberg-Jessen; Karina Christensen; Hanne Kjær Offenberg; Annette Bartels; Tanja Dreehsen; Steinbjørn Hansen; Henrik Daa Schrøder; Nils Brunner; Bjarne Winther Kristensen

doi:10.1007/s11060-009-9910-8

Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival

Charlotte Aaberg-Jessen, Karina Christensen, Hanne Kjær Offenberg, Annette Bartels, Tanja Dreehsen, Steinbjørn Hansen, Henrik Daa Schrøder, Nils Brunner, Bjarne Winther Kristensen

52 Citations (Scopus)

Abstract

In colorectal cancer and breast cancer a high TIMP-1 level has been shown to correlate with a shorter overall patient survival and it has been suggested that TIMP-1 is involved in tumour invasion, proliferation and apoptosis in different types of cancers. TIMP-1 is known to be expressed in gliomas but whether TIMP-1 is a prognostic marker in gliomas has not previously been investigated. In the present study, the TIMP-1 expression was investigated immunohistochemically in 112 formalin-fixed paraffin embedded astrocytomas and related to tumour grade and overall patient survival by scoring the TIMP-1 immunoreactivity of both tumour cells and blood vessels. Moreover, TIMP-1 in situ hybridisation was performed on ten of the glioblastomas. In the vast majority of the tumours TIMP-1 protein was expressed in both tumour cells and blood vessels. In situ hybridisation for TIMP-1 mRNA on glioblastomas confirmed the immunohistochemical expression of TIMP-1. The percentage of TIMP-1 positive tumour cells and blood vessels as well as the staining intensity varied between tumours of the same grade, but the total staining score increased with tumour grade. The multivariate Cox regression test showed that glioblastoma patients with the lowest TIMP-1 expression had a significantly longer overall survival (HR (95% CI) = 3.2 (1.5-6.7), P = 0.004) when compared to the patients with higher TIMP-1 protein expression. In conclusion, this study showed that low TIMP-1 immunohistochemical expression predicts longer overall survival in glioblastoma patients, suggesting a role for TIMP-1 as a biomarker in glioblastoma.

Original language	English
Journal	Journal of Neuro-Oncology
Volume	95
Issue number	1
Pages (from-to)	117-128
Number of pages	12
ISSN	0167-594X
DOIs	https://doi.org/10.1007/s11060-009-9910-8
Publication status	Published - 2009

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10.1007/s11060-009-9910-8

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@article{b7dcd450208b11df8ed1000ea68e967b,

title = "Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival",

abstract = "In colorectal cancer and breast cancer a high TIMP-1 level has been shown to correlate with a shorter overall patient survival and it has been suggested that TIMP-1 is involved in tumour invasion, proliferation and apoptosis in different types of cancers. TIMP-1 is known to be expressed in gliomas but whether TIMP-1 is a prognostic marker in gliomas has not previously been investigated. In the present study, the TIMP-1 expression was investigated immunohistochemically in 112 formalin-fixed paraffin embedded astrocytomas and related to tumour grade and overall patient survival by scoring the TIMP-1 immunoreactivity of both tumour cells and blood vessels. Moreover, TIMP-1 in situ hybridisation was performed on ten of the glioblastomas. In the vast majority of the tumours TIMP-1 protein was expressed in both tumour cells and blood vessels. In situ hybridisation for TIMP-1 mRNA on glioblastomas confirmed the immunohistochemical expression of TIMP-1. The percentage of TIMP-1 positive tumour cells and blood vessels as well as the staining intensity varied between tumours of the same grade, but the total staining score increased with tumour grade. The multivariate Cox regression test showed that glioblastoma patients with the lowest TIMP-1 expression had a significantly longer overall survival (HR (95% CI) = 3.2 (1.5-6.7), P = 0.004) when compared to the patients with higher TIMP-1 protein expression. In conclusion, this study showed that low TIMP-1 immunohistochemical expression predicts longer overall survival in glioblastoma patients, suggesting a role for TIMP-1 as a biomarker in glioblastoma.",

author = "Charlotte Aaberg-Jessen and Karina Christensen and Offenberg, {Hanne Kj{\ae}r} and Annette Bartels and Tanja Dreehsen and Steinbj{\o}rn Hansen and Schr{\o}der, {Henrik Daa} and Nils Brunner and Kristensen, {Bjarne Winther}",

note = "Keywords: Adult; Aged; Analysis of Variance; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Regression Analysis; Survival Analysis; Tissue Inhibitor of Metalloproteinase-1; Young Adult",

year = "2009",

doi = "10.1007/s11060-009-9910-8",

language = "English",

volume = "95",

pages = "117--128",

journal = "Journal of Neuro-Oncology",

issn = "0167-594X",

publisher = "Springer",

number = "1",

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T1 - Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival

AU - Aaberg-Jessen, Charlotte

AU - Christensen, Karina

AU - Offenberg, Hanne Kjær

AU - Bartels, Annette

AU - Dreehsen, Tanja

AU - Hansen, Steinbjørn

AU - Schrøder, Henrik Daa

AU - Brunner, Nils

AU - Kristensen, Bjarne Winther

N1 - Keywords: Adult; Aged; Analysis of Variance; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Regression Analysis; Survival Analysis; Tissue Inhibitor of Metalloproteinase-1; Young Adult

PY - 2009

Y1 - 2009

N2 - In colorectal cancer and breast cancer a high TIMP-1 level has been shown to correlate with a shorter overall patient survival and it has been suggested that TIMP-1 is involved in tumour invasion, proliferation and apoptosis in different types of cancers. TIMP-1 is known to be expressed in gliomas but whether TIMP-1 is a prognostic marker in gliomas has not previously been investigated. In the present study, the TIMP-1 expression was investigated immunohistochemically in 112 formalin-fixed paraffin embedded astrocytomas and related to tumour grade and overall patient survival by scoring the TIMP-1 immunoreactivity of both tumour cells and blood vessels. Moreover, TIMP-1 in situ hybridisation was performed on ten of the glioblastomas. In the vast majority of the tumours TIMP-1 protein was expressed in both tumour cells and blood vessels. In situ hybridisation for TIMP-1 mRNA on glioblastomas confirmed the immunohistochemical expression of TIMP-1. The percentage of TIMP-1 positive tumour cells and blood vessels as well as the staining intensity varied between tumours of the same grade, but the total staining score increased with tumour grade. The multivariate Cox regression test showed that glioblastoma patients with the lowest TIMP-1 expression had a significantly longer overall survival (HR (95% CI) = 3.2 (1.5-6.7), P = 0.004) when compared to the patients with higher TIMP-1 protein expression. In conclusion, this study showed that low TIMP-1 immunohistochemical expression predicts longer overall survival in glioblastoma patients, suggesting a role for TIMP-1 as a biomarker in glioblastoma.

AB - In colorectal cancer and breast cancer a high TIMP-1 level has been shown to correlate with a shorter overall patient survival and it has been suggested that TIMP-1 is involved in tumour invasion, proliferation and apoptosis in different types of cancers. TIMP-1 is known to be expressed in gliomas but whether TIMP-1 is a prognostic marker in gliomas has not previously been investigated. In the present study, the TIMP-1 expression was investigated immunohistochemically in 112 formalin-fixed paraffin embedded astrocytomas and related to tumour grade and overall patient survival by scoring the TIMP-1 immunoreactivity of both tumour cells and blood vessels. Moreover, TIMP-1 in situ hybridisation was performed on ten of the glioblastomas. In the vast majority of the tumours TIMP-1 protein was expressed in both tumour cells and blood vessels. In situ hybridisation for TIMP-1 mRNA on glioblastomas confirmed the immunohistochemical expression of TIMP-1. The percentage of TIMP-1 positive tumour cells and blood vessels as well as the staining intensity varied between tumours of the same grade, but the total staining score increased with tumour grade. The multivariate Cox regression test showed that glioblastoma patients with the lowest TIMP-1 expression had a significantly longer overall survival (HR (95% CI) = 3.2 (1.5-6.7), P = 0.004) when compared to the patients with higher TIMP-1 protein expression. In conclusion, this study showed that low TIMP-1 immunohistochemical expression predicts longer overall survival in glioblastoma patients, suggesting a role for TIMP-1 as a biomarker in glioblastoma.

U2 - 10.1007/s11060-009-9910-8

DO - 10.1007/s11060-009-9910-8

M3 - Journal article

C2 - 19430729

SN - 0167-594X

VL - 95

SP - 117

EP - 128

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

IS - 1

ER -

Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival

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